Gabriele Casirati
Dana-Farber Cancer Institute, Boston, MA, USA, and Boston Children’s Hospital, Boston, MA, USA
Essay
To target, to escape, perchance to cure
Borrowing a page from cancer’s playbook, scientists learn to evade their own therapies
DOI: 10.1126/science.adt9029
MOLECULAR MEDICINE
Abstract
Targeted cellular therapies hold tremendous potential to revolutionize cancer treatment, as demonstrated by the recent success of several immunotherapeutic agents. Despite this, harnessing the “different from normal” is not always possible, as several tumors do not bear cancer-restricted features that may be safely amenable to elimination without incurring on-target/off-tumor toxicity. In this essay, we describe the development of epitope editing, a gene-editing strategy to enable targeted immunotherapies in the context of hematological malignancies, by endowing healthy stem cells with selective resistance to chimeric antigen receptor T cells or monoclonal antibodies. We anticipate that this approach will provide opportunities to treat difficult-to-treat tumors, enable safer, non-genotoxic conditioning for bone marrow transplantation and broaden the therapeutic index of several pharmacological agents.
Biography
Gabriele Casirati received a medical degree from the Università degli Studi di Milano and a PhD from the Università degli Studi di Milano-Bicocca. He is currently researching immune engineering at the Dana-Farber Cancer Institute and Boston Children’s Hospital.